chr3-3805347-A-G

Variant names:

• chr3-3805347-A-G
• rs10780025
• NM_020873.7:c.-279+5428A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020873.7(LRRN1):​c.-279+5428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,166 control chromosomes in the GnomAD database, including 8,431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8431 hom., cov: 33)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796
• Publications: 3 publications found

Genes affected

LRRN1 (HGNC:20980): (leucine rich repeat neuronal 1) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SUMF1 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7	c.-279+5428A>G		intron_variant	Intron 1 of 1	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2	c.-279+4101A>G		intron_variant	Intron 2 of 2		NP_001311117.1
LRRN1	NM_001324189.2	c.-279+4101A>G		intron_variant	Intron 2 of 2		NP_001311118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRN1	ENST00000319331.4	c.-279+5428A>G		intron_variant	Intron 1 of 1	1	NM_020873.7	ENSP00000314901.3
SUMF1	ENST00000448413.5	n.*343-16273T>C		intron_variant	Intron 11 of 12	2		ENSP00000404384.1
LRRN1	ENST00000496115.1	n.376+4101A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43962 AN: 152048 Hom.: 8410 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 44037 AN: 152166 Hom.: 8431 Cov.: 33 AF XY: 0.293 AC XY: 21767 AN XY: 74410

African (AFR) AF: 0.501 AC: 20763 AN: 41484

American (AMR) AF: 0.273 AC: 4179 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2908 AN: 5170

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4820

European-Finnish (FIN) AF: 0.0928 AC: 984 AN: 10600

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11218 AN: 67998

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.211 Hom.: 16593

Bravo AF: 0.311

Asia WGS AF: 0.501 AC: 1742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10780025; hg19: chr3-3847031;